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Charles Q. Yu, Joyce K. Ho, Y. Joyce Liao; Laser-Assisted Transplantation of Stem Cells into the Adult Eye. Invest. Ophthalmol. Vis. Sci. 2011;52(14):2230.
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Regenerative approach to treat anterior ischemic optic neuropathy is of sound rationale and significant clinical demand because the central nervous system has limited repair and regenerative capacity and there are no effective neuron- or nerve-protective methods to treat this devastating condition. However, stem cell transplantation into the adult eye to reconstitute neurons and neural circuitry is difficult and often of low yield. In our study, we tested the potential benefit of retinal laser photocoagulation, a clinically proven form of controlled injury used to treat patients with diabetic retinopathy, on intravitreal stem cell transplantation into the adult eye.
We performed unilateral retinal laser photocoagulation in 130 adult wildtype 129 mice followed by bilateral intravitreal injection of enhanced green fluorescent protein (GFP)-expressing neural progenitor cells derived from murine embryonic stem cells (ES-NPCs). Different laser parameters were tested to assess optimal conditions for transplantation. We analyzed the retina of lasered vs. unlasered eyes following transplantation at 2-weeks, 1-month, and 2-months with immunohistochemistry and morphometric analysis.
Retinal lasering led to a dramatic increase in the number of GFP-positive ES-NPCs at all time points. Lasering of twelve 100-micron spots at 300 mW was sufficient and most efficacious compared to 3 spots or lower power. Two months following transplantation, many GFP-positive ES-NPCs survived and integrated predominantly into the inner retina, expressing neuronal marker beta-tubulin or glial marker glial fibrillary acidic protein. Many ES-NPCs formed dense clusters which extended beta-tubulin-positive processes that coalesce to form bundles that projected into the posterior pole.
Our data provided strong evidence that retinal laser photocoagulation facilitated the intravitreal transplantation of a large number of ES-NPCs into the adult mammalian inner retina. This form of controlled injury provided a permissive environment for stem cell differentiation into the neuronal pathway and formation of nerve-like structure within the inner retina.
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